Tumour-Infiltrating Lymphocytes (TILs) in Breast Cancer: a Predictive or a Prognostic Marker?

Dushyanthen, Sathana; Savas, Peter; Willard-Gallo, Karen; Denkert, Carsten; Salgado, Roberto; Loi, Sherene

doi:10.1007/s12609-014-0178-4

Cited by 2 publications

(3 citation statements)

References 97 publications

(125 reference statements)

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“…Interestingly, when stratified based on the presence of CD8+ lymphocytes, a high infiltration of FOXP3+ cells trended towards reduced survival in TNBC patients with low numbers of CD8+ cells. These results suggest that CD8+ lymphocytes could be the main effectors of anti-tumor immune responses, and that the consistent correlation between FOXP3 positivity and cytotoxic lymphocytes may in part explain conflicting results reported in previous studies [8]. …”

Section: Discussionsupporting

confidence: 57%

“…However, the composition of the tumor immune microenvironment is very heterogeneous, and the functional significance of specific immune cell subpopulations remains poorly understood. Indeed, cytotoxic CD8+ T cells have been shown to be an independent favorable prognostic factor, while studies on CD4+ T helper and forkhead box protein 3 (FOXP3) + T regulatory cells have shown conflicting results [8]. …”

Section: Introductionmentioning

confidence: 99%

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An immune stratification reveals a subset of PD-1/LAG-3 double-positive triple-negative breast cancers

et al. 2016

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BackgroundStromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC.MethodsFormalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259). Results were validated in an independent cohort of patients with TNBC (n = 104). Stromal TILs were evaluated on hematoxylin-and-eosin-stained sections. The density of CD4+, CD8+, and FOXP3+ lymphocytes, and the expression of the immune checkpoints PD-1 and LAG-3, were assessed by immunohistochemical analysis.ResultsThe presence of elevated TILs positively correlated with the density of all T cell subtypes, especially cytotoxic CD8+ lymphocytes. We showed that increasing stromal TILs assessed as a continuous variable is an independent prognostic marker of prolonged relapse-free survival and overall survival in TNBC. Among immune subpopulations, CD8+ lymphocytes are the main effectors of anti-tumor immune responses. In two independent cohorts, we found that PD-1 and LAG-3 were concurrently expressed in approximately 15% of patients with TNBC. The expression of both checkpoint receptors positively correlated with the presence of TILs, but was not significantly associated with patient outcome.ConclusionsOverall, our data indicate that the evaluation of stromal TILs remains the most reliable immune prognostic marker in TNBC, and support the clinical evaluation of anti-PD-1/PD-L1 and anti-LAG-3 in a subset of patients with TNBC who have concurrent expression of both checkpoint receptors.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0783-4) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

An immune stratification reveals a subset of PD-1/LAG-3 double-positive triple-negative breast cancers

et al. 2016

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“…In addition, low density of CD3+, CD4+, and CD8+ cells may increase the risk of relapse in squamous cell cervical cancer (Nedergaard et al, 2007). Further, higher numbers of CD3+, CD4+, and CD8+ tumor-infiltrating lymphocytes (TILs) is a predictor of extended survival in patients with infiltrating ductal carcinoma of the breast (Dushyanthen et al, 2015). In this study, the expression of CD3+ and CD4+ was correlated to tumor infiltration and metastasis.…”

Section: Discussionmentioning

confidence: 70%

Changes in T-lymphocytes in lung cancer patients after hyperthermic intraperitoneal chemotherapy or radiotherapy

Yan

Shi

et al. 2016

Genet. Mol. Res.

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ABSTRACT.We investigated dynamic changes in T-lymphocyte subsets after hyperthermic intraperitoneal chemotherapy (HIPEC) or radiotherapy using flow cytometry. A total of 1423 lung cancer patients admitted to our hospital between October 2012 and July 2015 were enrolled, and age-matched healthy individuals served as controls. Peripheral blood mononuclear cells (PBMCs) were purified using standard Ficoll density gradient centrifugation, based on which CD3+, CD4+, and CD8+ T-cells were isolated. A surface marker was identified by flow cytometry. Immunohistochemical analysis determined the distribution of the cells in the tumor mass or adjacent tissues. A total of 957 patients (male: 555; female: 402; median age: 49.3 years) with lung cancer who had received only HIPEC or radiotherapy were enrolled. The patients were followed-up until death. No statistical difference was noticed between the patients who had received chemotherapy compared with the baseline levels. A remarkable elevation was noticed in the CD3+ T-cells in the patients three months after radiotherapy (78.71 ± 9.36 vs 68.15 ± 9.65, P < 0.05). The level of CD8+ in the patients who had received chemotherapy or radiotherapy was remarkably elevated in the post-treatment period (P < 0.05). The CD3+ and CD8+ T-cells were mainly expressed in the cytoplasm rather than in the adjacent tissues. The expression of CD3+ and CD4+ was correlated to tumor infiltration and metastasis. Remarkable elevation was noticed in the CD3+ T-cells in the patients three months after radiotherapy. The expression of CD3+ and CD4+ was negatively correlated to tumor infiltration and metastasis in non-small-cell lung cancer patients.

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Tumour-Infiltrating Lymphocytes (TILs) in Breast Cancer: a Predictive or a Prognostic Marker?

Cited by 2 publications

References 97 publications

An immune stratification reveals a subset of PD-1/LAG-3 double-positive triple-negative breast cancers

An immune stratification reveals a subset of PD-1/LAG-3 double-positive triple-negative breast cancers

Changes in T-lymphocytes in lung cancer patients after hyperthermic intraperitoneal chemotherapy or radiotherapy

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